Rheumatoid Arthritis (RA) is a chronic systemic disease with hallmark pathological features localized primarily in the joints. The disease afflicts at least 1% of the U.S. population. RA is thought to be autoimmune in origin, and the complex nature of the pathophysiology remains to be completely delineated. Although all of the relevant autoantigens have not been characterized, recent studies have focused on the therapeutic potential of using oral tolerization to type II collagen to treat RA. Oral tolerization is a process by which oral administration of an antigen leads to a reduction in the immune response of the host against the antigen. Studies using oral administration of CII in animal models of RA and in early clinical trials have suggested that this strategy may be of benefit. The long term goal in this project is to develop an oral composite nanoparticle formulation that will diminish or reverse the autoimmune- mediated manifestations in an animal model of human RA. The particles will contain (1) a mammalian expression plasmid that encodes viral IL- 10, a key cytokine that has many immunosuppressive and anti- inflammatory properties and (2) type II collagen. We hypothesize that the overexpression of the cytokine in the intestinal immune system combined with intestinal delivery of CII will be more effective in driving tolerization to type II collagen than simple oral administration of CII. PROPOSED COMMERCIAL APPLICATIONS: More than one million people in the US are afflicted with rheumatoid arthritis. The proposed technology will provide a safer, more effective means of treatment of rheumatoid arthritis. Importantly, the concept of vIL-10 overexpression in the intestinal immune system in conjunction with antigen delivery for the purpose of driving oral tolerization may have utility in treatment of other debilitating diseases (e.g., multiple sclerosis) that are thought to arise from a malfunction of the host immune system.